Search for: rheumatoid arthritis    methotrexate    autoimmune disease    biomarker    gene expression    GWAS    HLA genes    non-HLA genes   

ID PMID Title PublicationDate abstract
9098440 Indications of an autoimmune component in LP(a) associated disorders. 1994 Oct The exceptionally strong independent association found between Lp(a) lipoprotein [Lp(a)] levels and atherosclerotic disorders indicate that Lp(a) is a factor of considerable importance in the pathogenesis of atherosclerosis. The association between Lp(a) and diabetes, rheumatoid arthritis and renal diseases suggest that Lp(a) may be involved in immunological mechanisms. Lp(a) has a great tendency to aggregate and bind to glucosaminoglycans, fibrin and fibronectin and is preferentially retained in the extracellular matrix during development of atherosclerosis and is in vitro phagocytosed by macrophages, probably as small aggregates. It was previously found that the Lp(a) level is significantly related to the HLA class II genotype in male patients with early coronary artery disease. In this paper additional results of interleukin determinantions in relation to HLA type and Lp(a) levels are presented and discussed. It is suggested that an autoimmune process, perhaps triggered by a concomitant intracellular infection may occur, especially in patients with inherited high Lp(a) levels in combination with certain inherited HLA class II genotypes.
8052076 Methotrexate therapy for autoimmune hearing loss: a preliminary report. 1994 Aug The management of autoimmune sensorineural hearing loss (SNHL) continues to challenge the otologist. Steroids and cyclophosphamide, the two traditional medications for this malady, are often associated with serious adverse reactions. In an effort to use a less toxic medication, the authors treated five autoimmune SNHL patients with low-dose oral methotrexate. Methotrexate has been found to be very effective in rheumatoid arthritis patients with acceptable adverse reactions. Preliminary results from this study indicate that methotrexate has the potential of being effective for autoimmune SNHL and associated otologic symptoms. Tolerance has been very good and side effects have been minimal.
7858116 Human Th1 and Th2 cells: functional properties, regulation of development and role in auto 1994 Evidence has accumulated suggesting the existence in humans of polarized T helper (Th) cell subsets, coded as Th1 and Th2, with defined cytokine secretion profiles. Immune responses to intracellular bacteria and viruses result in the preferential development of the Th1 cell subset. Th1 cells express cytolytic activity against antigen-presenting cells and provide helper function for IgM, IgG and IgA synthesis only at low T/B cell ratios. In contrast, Th2 cells develop in response to allergens or helminth antigens, provide help for all immunoglobulin classes, including IgE, and lack cytolytic potential. The cytokine milieu in the microenvironment plays a fundamental role in determining the functional phenotype of the subsequent antigen-specific Th1 or Th2 responses. In recent years it has become clear that Th1 and Th2 cells play different roles not only in protection against exogenous offending agents, but also immunopathology. Th2 cells are involved in immunopathology induced by helminths and are responsible for the initiation and maintenance of allergic disorders. Th1 cells seem to be involved in contact dermatitis, acute allograft rejection and organ-specific autoimmunity, such as thyroid autoimmune disorders, diabetes mellitus or multiple sclerosis, whereas less polarized patterns of Th cells are detectable in target organs of patients with rheumatoid arthritis. Sjogren's syndrome or systemic lupus erythematosus.
8290725 CT evaluation of amyloidosis: spectrum of disease. 1993 Nov Amyloidosis is a rare systemic disease caused by extracellular deposition of an insoluble protein. Although it is usually seen in a systemic form, 10%-20% of cases can be localized. Systemic amyloidosis is subclassified into an idiopathic primary form and a secondary or reactive form. Patients with primary amyloidosis have no underlying condition or disease. Men are affected more than women, and the mean age at presentation is 55-60 years. Some causes of secondary amyloidosis are multiple myeloma (10%-15%), rheumatoid arthritis (20%-25%), tuberculosis (50%), or familial Mediterranean fever (26%-40%). Radiographic studies of 90 patients with biopsy-proved primary or secondary amyloidosis were reviewed. Computed tomographic (CT) scans demonstrated a wide spectrum of disease in the cardiothoracic, gastrointestinal, genitourinary, and musculoskeletal systems. Amyloid deposition simulated both inflammatory and neoplastic conditions. Amorphous or irregular calcifications were occasionally identified within the amyloid deposit. Definitive diagnosis requires biopsy confirmation, as CT findings are nonspecific.
8515621 [Usefulness of DLco for the early diagnosis of pulmonary involvement in collagen diseases] 1993 Apr Collagen disease are chronic multisystemic disorders affecting many organs. Pulmonary involvement is frequently associated with these collagen diseases. The usefulness of the diffusion capacity of the lung for the early detection of pulmonary involvement was assessed in 182 collagen vascular disease patients. In addition, the clinical characteristics of those patients with pulmonary lesions were also evaluated. Among these, there were 69 cases of chronic rheumatoid arthritis (RA), 39 progressive systemic sclerosis (PSS), 24 systemic lupus erythematosus (SLE), 12 dermatomyositis-polymyositis (DM-PM), 12 mixed connective tissue disease (MCTD), 11 Sjögren syndrome (SS), 9 Behçet's disease (BD) and 6 unclassified connective tissue disease (UCTD). Patients with normal chest X-ray but with pulmonary dysfunction were recognized in 56% of RA, 59% of PSS, 50% of SLE, 50% of DM-PM, 71% of MCTD, 33% of SS, and 50% of BD cases. Moreover, a higher degree of immunological abnormalities was observed in those with pulmonary complications. From these results, we conclude that diffusion lung capacity is a useful index for the early diagnosis of pulmonary involvement in collagen vascular disorders.
8508048 Immunoglobulin genes in autoimmunity. 1993 The contribution of V germline genes and somatic mutation as well as the mechanism governing expression of the various V family genes in response to self-antigens are still unknown. Thus, we are still far from understanding the contribution and role of the B cell repertoire in human autoimmunity. Much of our current data on autoantibody gene repertoire are derived from laboratory generated hybridomas or animal model of autoimmune diseases. These may not reflect the human situation. In contrast, very few human autoantibodies with defined specificities have been structurally and genetically analyzed. In the future, meaningful data, perhaps from direct cloning and sequencing of autoantibodies derived from patients with autoimmune diseases, will be necessary to resolve issues in autoantibody repertoire usage. In this article, the prominent features of the human Ig repertoire, the usage of germline genes in autoantibodies, identifications of somatic mutations among autoantibodies and current data supporting either restricted or nonrestricted Ig gene usage and idiotypic expression among autoantibodies in several well-studied autoimmune diseases including systemic lupus erythematosus and rheumatoid arthritis are discussed.
1416562 The stress response and the regulation of inflammatory disease. 1992 Nov 15 The molecular and biochemical bases for interactions between the immune and central nervous systems are described. Immune cytokines not only activate immune function but also recruit central stress-responsive neurotransmitter systems in the modulation of the immune response and in the activation of behaviors that may be adaptive during injury or inflammation. Peripherally generated cytokines, such as interleukin-1, signal hypothalamic corticotropin-releasing hormone (CRH) neurons to activate pituitary-adrenal counter-regulation of inflammation through the potent antiinflammatory effects of glucocorticoids. Corticotropin-releasing hormone not only activates the pituitary-adrenal axis but also sets in motion a coordinated series of behavioral and physiologic responses, suggesting that the central nervous system may coordinate both behavioral and immunologic adaptation during stressful situations. The pathophysiologic perturbation of this feedback loop, through various mechanisms, results in the development of inflammatory syndromes, such as rheumatoid arthritis, and behavioral syndromes, such as depression. Thus, diseases characterized by both inflammatory and emotional disturbances may derive from common alterations in specific central nervous system pathways (for example, the CRH system). In addition, disruptions of this communication by genetic, infectious, toxic, or pharmacologic means can influence the susceptibility to disorders associated with both behavioral and inflammatory components and potentially alter their natural history. These concepts suggest that neuropharmacologic agents that stimulate hypothalamic CRH might potentially be adjunctive therapy for illnesses traditionally viewed as inflammatory or autoimmune.
1409881 The efficacy of laser therapy for musculoskeletal and skin disorders: a criteria-based met 1992 Jul The efficacy of laser therapy for musculoskeletal and skin disorders has been assessed on the basis of the results of 36 randomized clinical trials (RCTs) involving 1,704 patients. For this purpose, a criteria-based meta-analysis that took into account the methodological quality of the individual trials was used. The studies with a positive outcome were generally of a better quality than the studies with a negative outcome. No clear relationship could be demonstrated between the laser dosage applied and the efficacy of laser therapy, or between the dosage and the methodological score. In general, the methodological quality of these studies appeared to be rather low. Consequently, no definite conclusions can be drawn about the efficacy of laser therapy for skin disorders. The efficacy of laser therapy for musculoskeletal disorders seems, on average, to be larger than the efficacy of a placebo treatment. More specifically, for rheumatoid arthritis, posttraumatic joint disorders, and myofascial pain, laser therapy seems to have a substantial specific therapeutic effect. Further RCTs, avoiding the most prevalent methodological errors, are needed in order to enable the benefits of laser therapy to be more precisely and validly evaluated.
1575576 Antibody to a 63 kilodalton insect protein in ankylosing spondylitis. 1992 Mar Ankylosing spondylitis (AS) is associated with antibodies to a heat shock puff on drosophila chromosomes. This observation was investigated by immunoblotting using extracts of the Schneider insect cell line and HeLa cells, before and after heat shock. An insect protein of 63 kilodaltons (but no equivalent human protein) was recognised by 21 (46%) of 46 serum samples from patients with AS, one of two patients with Reiter's syndrome, four (7%) of 60 patients with systemic lupus erythematosus, and two (4%) of 50 control subjects, but not by serum samples from patients with rheumatoid arthritis (RA). Previous heat shock did not appear to affect the strength of reaction, but ML-30, a monoclonal antibody to the mycobacterial 65 kilodalton heat shock protein (hsp65), also recognised an insect protein of 63 kilodaltons by immunoblotting. Antibodies to recombinant mycobacterial hsp65 were measured by enzyme linked immunosorbent assay (ELISA) in serum samples from patients with AS and RA. IgA binding to hsp65 was increased in 41% of AS and 19% of RA serum samples, but there was no correlation with detection of antibody to the insect 63 kilodalton protein.
1557307 Future use and development of prenatal diagnosis. Consumers' attitudes. 1992 Jan The rapid progress of prenatal diagnosis and genetic tests makes it important to investigate attitudes towards this development. A total of 40 women and 20 men with personal experience of prenatal diagnosis for chromosome aberrations were interviewed about their moral opinion of the development. The majority (88 per cent) considered it certain or probable that all new methods developed will also be used in the future. The majority (62 per cent) were hesitant about testing for common disorders, e.g., diabetes mellitus and rheumatoid arthritis, but regarded it justified in some situations. One-third of the individuals (31 per cent) wanted some kind of restrictions for the use of the tests, but only 13 per cent recommended legislation for this purpose. The majority (84 per cent) believed that ethical principles are influenced by scientific progress. In most aspects, the women and their partners had similar attitudes. However, 82 per cent of the women but only 20 per cent of the men considered that the couple itself should decide about prenatal diagnosis. The results demonstrated a considerable respect regarding the difficult choices associated with the development of prenatal diagnosis, also among those who have decided favour of the test. The study indicated a greater need for autonomy among women than among men.
1385042 Molecular aspects of autoimmunity: a review. 1992 Molecular genetic techniques are being widely applied to the study of autoimmune diseases. Major advances have been made in diabetes, rheumatoid arthritis and coeliac disease. Work on experimental models of autoimmune uveitis suggests that similar advances will follow in this field. The application of molecular genetics to the study of immunology has lead to great advances in our understanding of the anatomy of antigen recognition. This work has lead to the identification of some of the structural determinants of antigen binding by MHC molecules and is helping to explain some MHC-disease associations. More recently, molecular studies of the T cell receptor have characterized patterns of T cell receptor expression in humans and have lead to the identification of regions of the T cell receptor critical for antigen recognition. These techniques will hopefully provide insights into the nature of autoimmunity and permit the identification of targets for disease specific immunotherapies. This review describes attempts to corelate MHC structure and function in the context of autoimmunity and discusses some of the strategies for analyzing T cell receptor usage in autoimmune disease.
27405837 In vitro antioxidant properties of the iron chelator pyridoxal isonicotinoyl hydrazone and 1995 Nov Since there are several problems with desferrioxamine (DFO) therapy, pyridoxal isonicotinoyl hydrazone (PIH) has been studied for more than 10 years as a promising new candidate for iron chelation therapy in iron-overload diseases. Iron chelation could also be helpful for experimental treatment of several other pathologies including rheumatoid arthritis and heart ischemia/reperfusion, due to the generation of oxyradicals and lipid peroxidation mediated by delocalized iron. We demonstrate here that sub-millimolar levels of PIH can inhibit the Fe(III)-EDTA/ascorbate-mediated formation of hydroxyl-like radicals as tested by the release of ethylene from 2-keto-4-methylthiobutyric acid (KMB assay) and the formation of malonaldehyde from 2-deoxyribose damage. PIH could also decrease the rates of Fe(III)-EDTA-mediated oxidation of ascorbate and block the peroxidation of liposomes of rat brain phospholipids induced by ferrous iron-EDTA. In all cases the in vitro antioxidant effectiveness of PIH was comparable to its analogs-including salicylaldehyde isonicotinoyl hydrazone-and to DFO. We conclude that PIH and its analogs are effective new candidates against iron-mediated oxidative stress for use in experimental medicine.
8892091 Analysis of naturally processed peptides eluted from HLA DRB1*0402 and *0404. 1996 Sep 15 Understanding the structural features of naturally processed peptides found within the major histocompatibility complex (MHC) class II peptide binding groove from disease-associated MHC molecules may provide insights into the nature of potential disease-related antigens. Class II MHC/peptide complexes were purified by immunoaffinity from transformed B cell lines homozygous for DRB1*0404 (an allele associated with rheumatoid arthritis) and *0402 (a closely related allele not associated with this disease). Peptides were eluted at acidic pH, fractionated by reversed phase HPLC, and analyzed by capillary electrophoresis. Those fractions containing a single dominant peptide were sequenced by automated Edman degradation and tandem mass spectrometry. The predominant peptide species identified came from non-polymorphic regions of the HLA class I molecules expressed by each cell line. Peptides from DRB1*0404 were found to be nested clusters derived from positions 26-43 of the HLA-B and -C alpha-chain. DRB1*0402 contained as the predominant peptide species a nested cluster from positions 129-145 of the HLA-B alpha-chain. The primary structure of the class I derived peptides was consistent with that seen by peptides exhibiting promiscuous DR binding behavior. Processing of MHC-derived peptides by MHC class II molecules is a common occurrence in the transformed B cell lines analyzed.
7654802 The Short Form-36 is preferable to the SIP as a generic health status measure in patients 1995 Sep OBJECTIVE: To assess the comparative usefulness of the Short Form-36 (SF-36) and the Sickness Impact Profile, (SIP) as generic health status measures in total hip arthroplasty. METHODS: Analysis of preoperative and 3-month data of 54 consecutive patients undergoing total hip replacement for osteoarthritis or rheumatoid arthritis. Instruments were mailed to patients preoperatively and 3 months postoperatively. RESULTS: In 10 of the 12 SIP subscales, but just 1 of the 8 SF-36 subscales, more than 40% of the patients had scores of zero. On a 100-point scale, the median global SIP was 12 (range 0-40) whereas the median global SF-36 was 50 (range 10-85). This indicates that many items of the SIP were not germane to patients undergoing joint arthroplasty. The global and, particularly, the physical dimensions of the SF-36 were more responsive than their SIP counterparts, as measured both by the standardized response mean (1.26 and 0.88, respectively) and the correlation with self-perceived improvement in quality of life (r = 0.37 and 0.26, respectively). The SF-36, but not the SIP, discriminated between patients with relatively good physical performance at 3 months with respect to their ability to work, to play sports, or to garden. CONCLUSION: The SF-36 is briefer, more relevant, and more responsive than the SIP and is preferable as a generic health status measure in patients undergoing elective hip arthroplasty. The SF-36 should be tested in other populations as well as other conditions to determine whether it is a superior generic health status instrument for evaluative research in orthopedic surgery.
8431204 Interleukin-1-mediated phospholipid breakdown and arachidonic acid release in human synovi 1993 Feb OBJECTIVE: Interleukin-1 (IL-1), an important mediator contributing to joint destruction in rheumatoid arthritis, is known to stimulate the release of arachidonic acid (AA) and prostaglandin E2 (PGE2) from adherent synoviocytes. To study the intracellular pathways involved in these functions, we stimulated cultures of human synovial cells with recombinant IL-1 beta. METHODS: AA liberation was measured after labeling synovial cells with 3H-AA, and PGE2 levels were determined by high performance liquid chromatography or radioimmunoassay. Identification of 3H-AA-labeled phospholipids was performed by thin layer chromatography. Cell-associated phospholipase A2 (PLA2) enzymatic activity was determined by an assay with cell-free systems and exogenous substrates. RESULTS: Stimulation of synovial cells with recombinant IL-1 beta induced a decrease in phosphatidylcholine (PC), phosphatidylinositol (PI), and phosphatidylethanolamine (PE), and a marked increase in cell-associated PLA2 activity as compared with controls. In the presence of either quinacrine, an inhibitor of PLA2 pathway activation, or neomycin, which binds to PI mono- and biphosphate thus blocking their degradation by phospholipases, AA and PGE2 secretion were reduced in a dose-dependent manner. Kinetic studies revealed that quinacrine had little blocking activity on the IL-1-mediated AA release after 1 hour of stimulation but completely abolished it after 5 or 8 hours. In contrast, neomycin exerted a partial but significant inhibitory effect from the first hour of stimulation onward. Addition of quinacrine was also demonstrated to abolish the IL-1-induced hydrolysis of PC and PE but not PI, indicating that PC and PE are the preferred substrates for PLA2 enzymatic activity in human synovial cells. CONCLUSION: Our findings strongly suggest that AA and PGE2 production by IL-1-triggered synoviocytes are largely dependent upon PLA2-mediated hydrolysis of PC and PE and to a lesser extent upon the earlier degradation of PI.
1472127 Interactions of synovial fluid immunoglobulins with chondrocytes. 1992 Dec OBJECTIVE: To study the interaction of synovial fluid (SF) immunoglobulins with living chondrocytes, and to evaluate the relative contribution of type II collagen (CII) antibodies. METHODS: SF of patients with rheumatoid arthritis (RA), osteoarthritis (OA), and gout were incubated with isolated bovine articular chondrocytes. Ig binding was measured by flow cytometry and by quantitation with 125I-labeled anti-IgG and anti-IgM. Complement-dependent cytotoxicity was determined by 51Cr release. Immunoglobulin binding and cytotoxicity were compared between chondrocytes obtained from the superficial and from the deep cartilage zones. RESULTS: Significantly greater IgG and IgM binding was found with RA SF compared with OA or gout SF. Chondrocytes bound more Ig than did fibroblasts. The relative contribution of anti-CII antibodies to Ig binding was studied following absorption of the SF with bovine CII, and by incubation with bacterial collagenase-treated chondrocytes. There was a small but significant reduction in IgG and IgM binding with SF samples that were positive for anti-CII. RA SF exhibited modest, but significantly greater complement-dependent cytotoxicity than OA SF: Gel chromatography fractionation indicated that IgM antibodies were responsible for the cytotoxic activity. Additional studies showed that SF IgM antibodies bound preferentially to, and killed chondrocytes obtained from, the superficial layers of cartilage. CONCLUSION: Anti-CII antibodies contained in RA SF represent one of many antibody specificities reacting with chondrocyte membrane antigens. Chondrocyte-reactive SF antibodies may play an important pathogenic role in the processes leading to irreversible cartilage damage in RA. These deleterious effects appear to be exerted particularly on chondrocytes located near the articular surface of cartilage.
1447852 [A case of bucillamine-induced interstitial pneumonia]. 1992 Sep Bucillamine [N-(2-mercapto-2-methylpropionyl)-L-cysteine] is an anti-rheumatic drug which was developed in Japan. Interstitial pneumonia induced by bucillamine has been reported in two patients with rheumatoid arthritis. In this report, we describe another patient who developed bucillamine-induced interstitial pneumonia. In August 1990, a 53-year-old man was admitted because of fever, dry cough and dyspnea on exertion (DOE). Five months previously, he had noted polyarthritis, and treatment with bucillamine was started in May 1990. His polyarthritis improved about 2.5 months after starting bucillamine, but he developed fever, dry cough, and DOE in August 1990. Chest X-ray on admission showed diffuse acinar and interstitial shadows predominantly in the bilateral upper lung fields. Pulmonary function tests revealed decreased vital capacity and diffusing capacity. Arterial blood gas (ABG) analysis revealed moderate hypoxemia with PaO2 67 Torr. After stopping bucillamine, the fever, dry cough, and DOE improved gradually, and the abnormal shadows on chest X-ray and ABG analysis showed moderate improvements. Bronchoalveolar lavage studies showed that total cell counts and proportion of lymphocytes were increased, and CD4+/CD8+ ratio of T cell subsets was decreased to 0.56. Transbronchial lung biopsy specimen revealed lymphocytic alveolitis and mild interstitial thickening. Lymphocyte stimulation test to bucillamine was negative, but patch test with bucillamine was positive. From the patient's clinical course, laboratory data, and pathologic findings, we concluded that this is a case of bucillamine-induced interstitial pneumonia. After treatment with corticosteroid, his chest X-ray and pulmonary function test showed marked improvements.(ABSTRACT TRUNCATED AT 250 WORDS)
1634773 Human leukocyte activation antigen M6, a member of the Ig superfamily, is the species homo 1992 Aug 1 Peripheral granulocytes from rheumatoid arthritis and reactive arthritis patients were recently found to express higher levels of a newly defined Ag, termed M6, in comparison to granulocytes from healthy subjects. We present here the molecular characterization of M6 Ag and show that it is a novel human leukocyte activation-associated cell surface glycoprotein. Peripheral lymphocytes do not significantly express M6 Ag, however, it appears upon 3-day PHA-activated T blasts. On monocytes, which constitutively express M6 Ag, it is down-regulated on day 1 but re-induced on day 3 of granulocyte-macrophage CSF stimulation. SDS-PAGE analysis of M6 immunoprecipitates shows a single band of 54 kDa under nonreducing conditions that shifts to 65 kDa under reducing conditions. Endoglycosidase F treatment of M6 immunoprecipitate reveals that 50% of the M6 molecule is composed of N-linked carbohydrates. By modifying the COS cell cloning strategy, we have isolated cDNA clones encoding M6 Ag. M6 cDNA hybridizes with a single mRNA transcript of approximately 1.7 kb in Northern blotting. Comparison analysis of the M6 sequence indicates that M6 Ag is a member of the Ig superfamily and the species homologue of rat OX-47 Ag, mouse basigin (gp42), and chicken HT7 molecule. The highly conserved remarkable transmembrane domain suggests that the M6 Ag may be a component of a multichain complex in the plasma membrane.
1309559 Transforming growth factor-beta in synovial fluids modulates Fc gamma RII (CD16) expressio 1992 Jan 15 Mononuclear phagocytes in the synovium of patients with arthritis, in contrast to blood monocytes, were found to express a third receptor for the constant region of Ig (Fc gamma RIII), in addition to Fc gamma RI and Fc gamma RII. Previously identified on mature mononuclear phagocytes or phagocytes exposed to transforming growth factor-beta (TGF-beta) in vitro, this study documents the presence of Fc gamma RIII (CD16) expressing cells at an inflammatory site. Furthermore, the presence of CD16 on the majority of the LeuM3 (CD14) positive synovial monocytic cells could be mimicked by exposing blood monocytes to synovial fluids from patients with rheumatoid arthritis (17 of 19) and synovial fluids from patients with osteoarthritis (4 of 4). In additional studies, the soluble factor in inflammatory synovial fluids responsible for regulating CD16 expression was found to be consistent with the presence of TGF-beta. Inhibition of the activity in synovial fluids with a neutralizing antibody to TGF-beta confirmed a role for this peptide in synovial phagocytic cell CD16 expression. Moreover, signal transduction through CD16 on synovial phagocytes resulted in augmented extracellular release of superoxide anion that may contribute to tissue damage and other inflammatory sequelae. Identification of TGF-beta and its association with upregulation of CD16 at sites of chronic inflammation may provide insight into the destructive lesions associated with inflammatory arthropathies.
20470573 [Endoprosthesis of the shoulder joint designed by the authors - surgical technique.]. 1996 Endoprostheses of the shoulder joint are nowadays already standard procedures in the surgical repertoir of orthopaedic and traumatological departments. Indication for the operation are degenerative diseases with destruction of the articular surface, non-reconstructible fractures of the upper end of the humerus, in particular in elderly patients and tumours in the area of the proximal portion of the humerus. The main cause of inadequate function of endoprostheses of the shoulder joint is insufficiency of the rotator cuff. This may be due either to its primary destruction by the basic disease (e. g. rheumatoid arthritis) or imperfect reconstruction during surgery. The majority of authors use during reconstruction of the rotator cuff a simple procedure, i. e. suture to the proximal portion of the endoprosthesis. In some instances the implementation of the suture is difficult or there is the risk the stiches will cut through during rehabilitation. Favourable experience with reconstruction of the rotator cuff during non-anatomical reconstruction of fractures of the proximal humerus by screwing of the insertion lamellae of the greater and lesser tubercle made the authors try to use this principle in the construction of a new type of endoprosthesis, which is described in detail in the submitted paper. Subsequently the authors describe also differences in the surgical technique during implantation of the endoprosthesis in patients with degenerative diseases and in traumatological indications. In their opinion the advantage is that in traumatic indications of replacement of the shoulder joint the suggested implant makes reliable and relatively easy fixation of both tubercles with insertions of the rotator cuff to the endoprosthesis possible and simultaneously also attachment to the fragment of the diaphysis. In fragments of the greater tubercle this can be achieved by the use of a clawed splint which is fixed by one screw inserted via the corticalis of the diaphysis into the stem of the endoprosthesis. This ensures the stability of the endoprosthesis in the proximo-distal direction as well as against rotation. The fragment of the lesser tubercle is fixed by one screw to the body of the endoprosthesis. The authors assume that reconstruction of the rotator cuff and at the same time stabilization of the shank of the endoprosthesis by one screw and a clawed splint differs fundamentally and is a new approach to the solution of this very complicated problem. Despite the initial clinical experience the authors are aware of certain technical shortcomings of the implant and instrumentarium and continue to work on their elimination. Key words: endoprosthesis of the shoulder joint, reconstruction of the rotator cuff.